“How are you doing?”
This seems like such a simple (and obvious) question to ask patients during a clinical trial. But systematically collecting, analyzing and reporting data on how patients are doing is far from simple. The US Food and Drug Administration (FDA) highlighted many of the challenges in a pair of analyses of lung cancer trials presented in October 2019 at the 26th Annual Conference of the International Society for Quality of Life Research (ISOQOL).1,2
The analyses are among the latest in a long-running effort by researchers and regulatory agencies to make sense of patient-reported outcomes (PROs). For both studies, the FDA analyzed lung cancer clinical trials for drugs submitted for FDA approval from 2008 to 2017. The researchers determined that clinical trials varied greatly in how PRO research objectives were defined and how PRO findings were analyzed and presented. They concluded that standardizing this process could be the key to unlocking a treasure trove of patient-reported data that can guide clinical and regulatory decision making.
“Inappropriate statistical analysis of PROs can lead to biased interpretation of patient experience,” wrote an FDA spokesperson in an email to Cancer Therapy Advisor. “With the increased attention on appropriately evaluating PRO data, it was important to assess how PROs were currently being analyzed in lung cancer trials submitted to FDA to identify important statistical issues and potential solutions.”
PROs can help regulators, clinicians, and patients weigh whether a treatment’s side effects outweigh its benefits. Quality of life concerns are particularly important for lung cancer, the leading cause of cancer death in the United States.
Lung cancer PROs such as chest pain, labored breathing and coughing can be an early sign that a patient’s overall condition is worsening, said Carolyn Gotay, PhD, professor emerita of public health at the University of British Columbia, Vancouver. A 2008 study by Gotay and colleagues reported that PROs were associated with survival in 36 of 39 cancer clinical trials.3
“How patients are feeling and expressing their experience does seem to say something about how long they’re likely to live,” Dr Gotay said.
One of the FDA analyses presented at ISOQOL explored the connection between lung cancer PROs and clinical outcomes in 15 non-small cell lung cancer trials.4 The study measured the relationship between time-to-deterioration in cough, chest pain, and shortness of breath (dyspnea) and overall and progression-free survival. PROs correlated moderately with progression-free survival (Pearson correlation coefficient range, 0.3-0.89) and weakly with overall survival (0.29-0.61).
“[It’s] a little disappointing, but not totally unsurprising, to see the modest correlations between overall survival … and time to deterioration,” said Jeff Sloan, PhD, professor of biostatistics and of oncology at Mayo Clinic, Rochester, Minnesota, who was not involved in the study. “One of the things that we’ve seen that’s consistent over the years is patients are highly variable in their individual experiences.”